Showing papers by "Ravinder Reddy published in 2010"

Validation of sodium magnetic resonance imaging of intervertebral disc.

Abstract: Study Design.This study demonstrated the diagnostic potential of sodium (Na) magnetic resonance imaging (MRI) for noninvasive quantification of proteoglycan (PG) in the intervertebral discs.Objective.To determine the existence of a linear correlation between intervertebral disc [Na] measured from so

Rotating Frame Spin Lattice Relaxation in a Swine Model of Chronic, Left Ventricular Myocardial Infarction

Abstract: T1ρ relaxation times were quantified in a swine model of chronic, left ventricular myocardial infarction. It was found that there were low frequency relaxation mechanisms that suppress endogenous contrast at low spin-lock amplitudes and in T2-weighted images. A moderate amplitude spin-locking pulse could overcome these relaxation mechanisms. Relaxation dispersion data were measured over a range of RF field amplitudes, and a model was formulated to include dipole-dipole relaxation modulated by molecular rotation and an apparent exchange mechanism. These techniques may find some use in the clinic for the observation of chronic, left ventricular cardiac remodeling.

T1ρ MRI quantification of arthroscopically confirmed cartilage degeneration

Abstract: Nine asymptomatic subjects and six patients underwent T(1)rho MRI to determine whether Outerbridge grade 1 or 2 cartilage degeneration observed during arthroscopy could be detected noninvasively. MRI was performed 2-3 months postarthroscopy, using sagittal T(1)-weighted and axial and coronal T(1)rho MRI, from which spatial T(1)rho relaxation maps were calculated from segmented T(1)-weighted images. Median T(1)rho relaxation times of patients with arthroscopically documented cartilage degeneration and asymptomatic subjects were significantly different (P < 0.001), and median T(1)rho exceeded asymptomatic articular cartilage median T(1)rho by 2.5 to 9.2 ms. In eight observations of mild cartilage degeneration at arthroscopy (Outerbridge grades 1 and 2), mean compartment T(1)rho was elevated in five, but in all observations, large foci of increased T(1)rho were observed. It was determined that T(1)rho could detect some, but not all, Outerbridge grade 1 and 2 cartilage degeneration but that a larger patient population is needed to determine the sensitivity to these changes.

Magnetization transfer ratio mapping of intervertebral disc degeneration.

Abstract: The magnetization transfer ratio of the lumbar discs was spatially quantified from age-matched subjects and the nucleus pulposus magnetization transfer ratio was correlated with T2-weighted Pfirrmann grades. A moderate and significant linear correlation between magnetization transfer ratio and Pfirrmann grades was observed, suggesting that nucleus pulposus collagen relative density increases with degeneration. High-resolution axial magnetization transfer ratio maps revealed elevated magnetization transfer ratio in the nucleus pulposa of injured and heavily degenerated discs. In the injured disc, significant elevation in nucleus pulposa magnetization transfer ratio was not accompanied by significant decrease in disc height. This observation may suggest a possible increase in absolute collagen content, in addition to increased collagen relative density. In summary, magnetization transfer MRI of the disc may serve as a noninvasive diagnostic tool for disc degeneration, in addition to other MRI techniques specific to proteoglycan content.

Mapping of cerebral oxidative metabolism with MRI.

Abstract: Using a T1ρ MRI based indirect detection method, we demonstrate the detection of cerebral oxidative metabolism and its modulation by administration of the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) in a large animal model with minimum utilization of gas. The study was performed by inhalation in swine during imaging on clinical MRI scanners. Metabolic changes in swine were determined by two methods. First, in a series of animals, increased metabolism caused by DNP injection was measured by exhaled gas analysis. The average whole-body metabolic increase in seven swine was 11.9%+/-2.5% per mg/kg, stable over three hours. Secondly, hemispheric brain measurements of oxygen consumption stimulated by DNP injection were made in five swine using T1ρ MRI following administration of gas. Metabolism was calculated from the change in the T1ρ weighted MRI signal due to H217O generated from inhalation before and after doubling of metabolism by DNP. These results were confirmed by direct oxygen-17 MR spectroscopy, a gold standard for in vivo H217O measurement. Overall, this work underscores the ability of indirect oxygen-17 imaging to detect oxygen metabolism in an animal model with a lung capacity comparable to the human with minimal utilization of expensive gas. Given the demonstrated high efficiency in use of and the proven feasibility of performing such measurements on standard clinical MRI scanners, this work enables the adaption of this technique for human studies dealing with a broad array of metabolic derangements.

Imaging cartilage physiology.

Abstract: Imaging the physiology of cartilage tissue holds promise for an early detection of osteoarthritis (OA), the most common joint disease whose prevalence will only increase due to an aging population (1). The disease is characterized by focal cartilage damage, changes in the subchondral bone, mild synovitis, and thickening of the joint capsule in synovial joints. Key to understanding the pathology of the disease is to appreciate that the biochemistry of cartilage tissue underlies its special purposes of control over joint loading and motion. Only a small fraction of the volume of cartilage is occupied by cells (chondrocytes) that facilitate construction, repair and degradation of the extracellular matrix (ECM) in response to stimuli. Water occupies 70% of the volume of the ECM (1) while the major solid constituents (Figure 1) are aggrecan (5% w/v) and type II collagen (20% w/v). Figure 1 Schematic of cartilage extracellular matrix (ECM). Sodium is incorporated in to the ECM to balance the fixed charge density (FCD) of negatively charged Chrondroitin Sulfate (CS) and Keratan Sulfate (KS) subgroups of the Aggrecan monomer, the main glycosaminoglycan ... The early stage of OA is associated with an increase in enzymatic degradation by matrix metalloproteinases resulting in glycosaminoglycan (GAG) aggrecan depletion and degradation of the collagen network. In cartilage, GAG side chains are made of continuously repeating disaccharides containing carboxyl and sulfate functional groups and are both negatively charged under physiological conditions. The negative charge GAG confers on cartilage is the fixed charge density (FCD). Gorton originally proposed a model for the physiology of connective tissues in which a high polysaccharide content induces an osmotic pressure that is resisted by the network of collagen (5). In this model, the presence of highly electronegative and immobile GAG macromolecules results in an influx of sodium ions to maintain electro-neutrality. Since then, Maroudas extended this model by introducing the Donnan equilibrium to describe the flux of charged ions across a semi-permeable membrane in the presence of a charged but non-exchanging GAG restricted to a single compartment (6,7). In this model, the low hydraulic permeability of GAG counterbalances resistive loads by its swelling pressure while collagen provides tensile and shear strength. Therefore, GAG loss in early OA initiates a cascade by which osmotic pressure is reduced and joint compression permanently disrupts the cartilage leading to thinning, fracturing and subsequently pain (8,9). Radiographic imaging is the current gold standard in imaging technology to detect advanced stages of OA. Lacking sensitivity to soft tissues, this x-ray based technique measures joint space narrowing (JSN) to indirectly gauge the extent of damage to cartilage. In addition, outcome instruments for assessment of OA in patients such as the Knee Injury and Osteoarthritis Outcome Score (KOOS), an extension of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), is also used to determine mobility and pain in a specific joint (2,3). However, radiography, along with nuclear medicine scans, arthrography, and computed tomography (CT) scans, are limited in their use because they are unable to detect early cartilage abnormalities (4). Conventional T1 and T2 MRI can directly visualize all diarthrodial tissues, including cartilage, bone, synovium, menisci, and ligaments and has substantial advantages over radiography (10-12). Due to the high morbidity of OA, therapeutic interventions are particularly necessary but current methods are restricted to management of pain and surgical interventions (13). However, improving outcomes require development of more effective interventions that can slow or reverse the course of the disease. In this context, there is a requirement for strong diagnostic information sensitive to the early stages of the disease, where cartilage appears intact on radiographs. The aim of this review is to highlight new MRI-based techniques that exploit spin dynamics between endogenous macromolecules of cartilage. These include T1ρ and T2 relaxometry, Chemical Exchange Saturation Transfer (CEST), Magnetization Transfer (MT), all proton-based MRI techniques, and sodium MRI. Most of these techniques have been developed to specifically detect the GAG component of cartilage, which is the more important element due to the ostensibly limited contribution of collagen to the initiating steps of OA (14). Only the salient features of these methods are described here with a limited literature review. The reader is referred to specialized reviews on each topic described. T1ρ Relaxometry T1ρ MRI is an alternative to conventional T1 and T2 MRI (15) by its use of a long-duration, low-power radiofrequency (RF) referred to as spin-lock (SL) pulse applied to the magnetization in the transverse plane. The magnetization is effectively spin-locked around an effective B1 field created by the vector sum of the applied B1 and any off-resonant component. The spin-locked magnetization will relax with a time constant T1ρ, the spin-lattice relaxation in the rotating frame, during the RF field. The B1 field attenuates the effect of dipolar relaxation, static dipolar coupling, chemical exchange and background gradients on the signal resulting in a T1ρ that is always greater than T2. T1ρ is influenced by the exchange of hydroxyl (–OH) and amide (–NH) protons on the PG side-chain (16). Quantitative T1ρ MRI relaxation maps (relaxometry) reflecting the biochemical composition of cartilage are created by fitting the signal intensity of T1ρ weighted MR images as a function of the duration of the SL pulse while the amplitude of SL pulse (γB1~0.1-few kHz) is fixed (15). In this manner, spatial maps of T1ρ values related to macromolecular composition of tissues can be visualized and analyzed. There has been considerable amount of work on biological tissues using T1ρ-spectroscopy and imaging dealing with tumors, muscle, myocardium, blood flow and cartilage (17-27). Several studies had reported that the non-averaged dipolar interaction between water protons associated with collagen is the predominant contributor to relaxation in cartilage (28). T1ρ-dispersion MRI, where the amplitude of the SL pulse amplitude is also varied, can be used to detect spectral density components in cartilage that are in the neighborhood of γB1. The effect of spin-locking reduces the laminar appearance in cartilage as demonstrated by Akella et al in an orientation-dependent MRI experiment of cartilage plugs (29). In this study, a typical laminar appearance was present in T2 MRI when the normal to the surface of cartilage was parallel to B0 but absent in T1ρ MRI of the same cartilage specimen. In addition, T1ρ values were consistently greater than T2 at all orientations throughout the cartilage layers, a result of spin-locking the magnetization. Several studies have demonstrated the efficacy of T1ρ MRI in detecting early tissue pathology with increasing values in OA-affected cartilage compared to normal tissue (30). T1ρ MRI was also demonstrated to quantitatively evaluate meniscus and cartilage matrix in animal models as well as in patients with acute anterior cruciate ligament (ACL) injuries (31,32). Studies on arthroscopically-confirmed early grades of chondromalacia have demonstrated the potential of T1ρ mapping method in detecting earliest molecular changes in cartilage in vivo (33). Recently, a multicenter study of OA subjects has shown that larger changes were observed in T1ρ compared to T2, cartilage volume, and thickness measurements (34) however, the reproducibility of T2 relaxometry was better than T1ρ.

Measurement of intervertebral disc pressure with T1ρ MRI

Abstract: The aim of this study is to demonstrate T1ρ MRI's capability for measuring intervertebral disc osmotic pressure. Self-coregistered sodium and T1ρ-weighted MR images were acquired on ex vivo bovine intervertebral discs (N = 12) on a 3 T clinical MRI scanner. The sodium MR images were used to calculate effective nucleus pulposus fixed-charge-density (mean = 138.2 ± 27.6 mM) and subsequently osmotic pressure (mean = 0.53 ± 0.18 atm), whereas the T1ρ-weighted images were used to compute T1ρ relaxation maps. A significant linear correlation (R = 0.56, P < 0.01) between nucleus pulposus fixed-charge-density and T1ρ relaxation time constant was observed. More importantly, a significant power correlation (R = 0.72, P < 0.01) between nucleus pulposus osmotic pressure as predicted by sodium MRI and T1ρ relaxation time constant was also observed. The current clinical method for assessing disc pressure is discography, which is an invasive procedure that has been shown to have negative effects on disc biomechanical and biochemical properties. In contrast, T1ρ MRI is noninvasive and can be easily implemented in a clinical setting due to its superior signal-to-noise ratio compared with sodium MRI. Therefore, T1ρ MRI may serve as a noninvasive clinical tool for the longitudinal evaluation of disc osmotic pressure. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.

T1 rho magnetic resonance imaging for staging of hepatic fibrosis

Abstract: Methods for diagnosis of fibrotic diseases, staging of fibrotic diseases and monitoring treatment of fibrosis. The presence of fibrotic tissue is detected. First, a T 1ρ relaxation time of tissue is determined using magnetic resonance imaging. The determined T 1ρ relaxation time is then compared to a baseline T 1ρ relaxation time indicative of healthy tissue, and the presence of fibrotic tissue is then determined based on results of said comparison step. To determine a stage of fibrosis, a T 1ρ relaxation time of tissue is determined and compared to one or more calibrated T 1ρ relaxation times indicative of one or more stages of fibrosis, and the stage of fibrosis is determined based on results of said comparison step. The proposed technology offers a non-invasive MRI technique based on T 1ρ contrast that is sensitive enough to detect small changes of ECM hepatic protein concentration and architecture in all stages of hepatic fibrosis.

Characterization of blood flow, oxygenation and metabolism under hypercapnia in swine

Abstract: We employed diffuse reflectance and correlation spectroscopies to monitor the response of cerebral oxygenation and blood flow to hypercapnia in swine, and compared the oxygen consumption optically estimated to direct MRI measurements.